Abstract

Background Despite the increasing interest in combination therapy for the treatment of cancer, controlled delivery of different therapeutics with high body-clearance efficacy and cancer cell specificity remained a great challenge. In this study, a novel codelivery system was synthesized through one-pot coordination-driven self-assembly of 2-methylimidazole, zinc ion and chemotherapeutic drug (doxorubicin, DOX), followed by a surface decoration of photothermal agent (indocyanine green, ICG). To improve the targeting specificity performance, folic acid-conjugated polyethylene glycol (FA-PEG) antennas was connected on the surface of nanoparticles.Results The hybrid nanoparticles keep stable under neutral physiological condition but decompose when exposed to acidic environment, resulting in the on-demand release of DOX and ICG for chemo-photothermal combined therapy. Moreover, by switching the initial large size (~ 94 nm) to an ultrasmall size (∼10 nm) in cancer cells, the nanoparticles hold great potential to avoid nanotoxicity for clinical applications.Conclusion sThis work provides a new strategy for co-delivery of different therapeutics for combined cancer therapy with high cancer cell specificity and low nanotoxicity.